The woodchuck hepatitis virus (WHV) is taxonomically and serologically related to the hepatitis B virus (HBV). Infection with each of these viruses is associated with acute and chronic hepatitis and hepatic cell carcinoma in their respective hosts and these associations appear to be etiological in nature. Thus, WHV infection of woodchucks provides a relevant and convenient model for understanding HBV infections of humans. Several lines of research have been pursued. First, we found that the WHV X gene is very sensitive to alterations and is essential for viral replication in animal transfection experiments. Second, fine mapping of the X transcript promoter was used to identify the essential nucleotides in this cis-acting element. Third, we have extended our previous experiments on the characterization of the bi-directional promoter of WHV. Fourth, two WHV isolates were shown to develop surface antigenemia and liver tumors at significantly different rates (this last finding has important implications for understanding the molecular mechanisms involved in viral replication and in the oncogenic potential of hepadnaviruses). Fifth, an in vitro cell culture system for transfection of WHV was developed. Sixth, the role of the capsid protein in viral replication was studied. Seventh, the role of the envelope proteins in viral replication was examined.